Peripheral Neuronal Mechanisms of Itch

瘙痒伴随许多神经、皮肤和全身疾病，并导致痛苦和损失。 生活质量。人类这种感觉背后的周围神经机制仍然很差 明白了。我们提案的总体目标是确定急性瘙痒和长期瘙痒的程度 瘙痒症是由皮肤伤害感受器的放电编码的。我们建议电生理学 在非人类灵长类动物中进行的实验，旨在表征以下亚型对瘙痒性化学刺激的反应 外周伤害性神经纤维和人类的补充、相关心理物理学研究 确定这些不同神经元群在瘙痒感中的作用。我们将测试以下预测 模型提出皮肤伤害感受器通过以下方式发出不同的瘙痒和痛觉刺激信号： 激活的传入神经的总数或其放电的速率或模式。在临床相关的 持续瘙痒模型，即过敏性接触性皮炎的SADBE模型，我们将研究 使用化学和热刺激自发瘙痒和增强瘙痒的神经机制 人类心理物理学研究和猴子伤害性传入的电生理记录。 通过研究急性和长期瘙痒，我们将能够首次识别发生的变化 周围神经系统处于临床相关的瘙痒状况。更好地了解伤害感受器如何 介导正常和瘙痒皮肤的瘙痒感会增加发生和瘙痒的可能性 评估新颖的外周作用药物，以减少慢性病引起的异常伤害感受器功能 痒。

Itch accompanies many neurological, dermatological and systemic diseases and leads to suffering and loss in the quality of life. The peripheral neuronal mechanisms underlying this sensation in human are still poorly understood. The overall goal of our proposal is to determine how acute itch and the prolonged itch from a pruritic disease are encoded in the discharges of cutaneous nociceptors. We propose electrophysiological experiments in nonhuman primate to characterize the responses to pruritic chemical stimuli in subtypes of peripheral nociceptive nerve fibers and complementary, correlative psychophysical studies in human to determine the role of these different neuronal populations in itch sensation. We will test the predictions of models that propose that cutaneous nociceptors differentially signal pruritic and algesic stimuli either by the overall number of afferents activated or by the rates or patterns of their discharges. In a clinically relevant model of prolonged itch, namely the SADBE model of allergic contact dermatitis, we will investigate the neuronal mechanisms of spontaneous itch and enhanced itch to chemical and heat stimuli using psychophysical studies in humans and electrophysiological recordings from nociceptive afferents in monkeys. By studying both acute and prolonged itch, we will be able to identify, for the first time, changes that occur in the peripheral nervous system in a clinically relevant itch condition. A better understanding of how nociceptors mediate the sensation of itch in normal and pruritic skin will increase the possibility of developing and evaluating novel, peripherally acting drugs that reduce the abnormal nociceptor function underlying chronic itch.